DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma.
DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma.
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作者：
Ju G;Zhou T;Zhang R;Pan X;Xue B;Miao S
双特异性蛋白磷酸酶（DUSP）12是蛋白酪氨酸磷酸酶家族的非典型成员，在多种类型的恶性肿瘤中过表达。该蛋白家族保护细胞免于凋亡，促进细胞增殖和运动。然而，DUSP12在肝细胞癌（HCC）中的病理作用尚不完全清楚。我们利用多个在线数据库分析了DUSP12 mRNA在HCC和正常肝组织中的表达，并利用cbiopportal数据库探索了DUSP12突变体的状态。利用肿瘤免疫估计资源数据库和肿瘤与免疫系统相互作用数据库证实了DUSP12表达与肿瘤浸润性免疫细胞之间的相关性。功能丧失试验用于评估DUSP12在HCC进展中的作用。与正常肝组织相比，HCC组织中DUSP12在mRNA扩增的同时表达更高，表明DUSP12表达越高，总生存期越短。差异表达基因的功能富集分析提示DUSP12调节HCC的发生，短发夹RNA （short hairpin, sh）敲低DUSP12表达可降低HCC细胞的增殖和迁移。此外，DUSP12的表达与CD4+ T细胞（尤其是CD4+调节性T细胞）、巨噬细胞、中性粒细胞和树突状细胞的浸润呈正相关。DUSP12的表达与免疫检查点部分呈正相关，并且在HCC的C3免疫亚组（存活时间最长）中下调。这些数据提示DUSP12可能在HCC的肿瘤发生、免疫细胞浸润和预后中起关键作用。
Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
3.7
作者：
Li Y;Zhu Z;Zhang S;Yu D;Yu H;Liu L;Cao X;Wang L;Gao H;Zhu M
通讯作者：
Zhu M
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS
影响因子：
3.7
作者：
Cain EL;Braun SE;Beeser A
通讯作者：
Beeser A